Carboplatin and Docetaxel Followed by Epstein-Barr Virus Cytotoxic T Lymphocytes (CADEN)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Texas Children's Hospital
The Methodist Hospital System
Center for Cell and Gene Therapy, Baylor College of Medicine
M.D. Anderson Cancer Center
Information provided by (Responsible Party):
Chrystal Louis, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00953420
First received: August 4, 2009
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

Patients have a type of cancer called nasopharyngeal carcinoma (NPC) that has either come back or not gone away after the best known standard treatments.

Most patients that respond to chemotherapy once their NPC tumors have come back have been treated with a platinum-based medication like cisplatin. However, since many patients are given cisplatin during their initial treatment for NPC, in this study, they will be treated with another platinum-based chemotherapy medicine that has been used in patients with NPC called carboplatin. In this study, carboplatin will be used in combination with another drug called docetaxel. Other studies in patients with advanced head and neck cancer have shown that docetaxel can cause tumors to respond better and allow patients to survive longer when added to the standard treatments for those diseases.

Some patients with NPC show evidence of infection with the virus that causes infectious mononucleosis, known as the Epstein Barr virus (EBV), before or at the time of their cancer diagnosis. EBV is found in the cancer cells of almost all patients with advanced stage disease, suggesting that it may play a role in causing NPC. Previously, patients have been treated with high-risk NPC using EBV-specific cytotoxic T cells. These cells are grown in the laboratory and taught to recognize and attack EBV infected cells. In the past, patients were either given the cells alone or just after they had received a medication to briefly lower their white blood cell count. In both cases, many patients had their tumors shrink and in some cases completely disappear after being treated with these EBV-specific cytotoxic T cells.

Investigators have now decided to look at how patients with NPC and their tumors respond to the treatment combination of chemotherapy and EBV-CTL. Patients are being asked to participate in this study since the NPC tumor is associated with EBV and has either come back or not responded to standard treatment. This combination of chemotherapy and EBV-CTLs is an investigational treatment not approved by the Food and Drug Administration.

The purpose of this study is to see how relapsed or refractory, EBV-associated NPC tumors respond when treated with carboplatin and docetaxel followed by EBV-CTL.


Condition Intervention Phase
Nasopharyngeal Carcinoma
Drug: Docetaxel
Drug: Carboplatin
Drug: Dexamethasone
Biological: EBV-specific cytotoxic T lymphocytes
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Carboplatin and Docetaxel Followed by Epstein-Barr Virus Cytotoxic T Lymphocytes in Patients With Refractory/Relapsed EBV-positive Nasopharyngeal Carcinoma(CADEN)

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • The primary endpoint of the study is to evaluate the overall response rate for patients with advanced-stage, relapsed/refractory, EBV positive nasopharyngeal carcinoma after re-induction chemotherapy and immunotherapy. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    The overall response rate for patients with advanced-stage, relapsed/refractory, EBV positive nasopharyngeal carcinoma after re-induction chemotherapy (treatment with docetaxel and carboplatin) followed by immunotherapy with EBV-specific Cytotoxic T lymphocytes will be measured. Response rates will be estimated as the percent of patients whose best response is a CR or PR, and a 95% confidence interval will be calculated for the fraction of responses obtained.To measure the overall response rate, disease will be determined by imaging (MRI, CT, and/or PET imaging) 8 weeks after immunotherapy. In addition, per standard of care, disease re-evaluation will continue 3 months during the first year after participation and then as clinically indicated per the patient's primary oncologist.


Secondary Outcome Measures:
  • Response to re-induction chemotherapy [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • Evaluation of immune response by measuring EBV-DNA levels [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: November 2009
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chemotherapy and Immunotherapy
  1. Docetaxel 60 mg/m2 IV on Day 1
  2. Carboplatin with target AUC of 5 (mg/ml x min) on Day 1
  3. Dexamethasone 5 mg/m2/dose (max of 8 mg/dose) po q hs on Day 0, and q am and hs on Day 1
  4. After cycle 1, subsequent cycles of chemotherapy may start once ANC > 1000 and platelets > 100,000 post nadir
  5. Up to an additional 2 cycles of chemotherapy, given per the above schedule, may be given if the EBV-specific cytotoxic T lymphocytes product is not available after the initial 4 cycles
Drug: Docetaxel
60 mg/m2 IV on Day 1
Other Name: Taxotere
Drug: Carboplatin
Target AUC of 5 (mg/ml x min) on Day 1
Other Name: Paraplatin
Drug: Dexamethasone
5 mg/m2/dose (max of 8 mg/dose) po q hs on Day 0, and q am and hs on Day 1
Other Name: Decadron
Biological: EBV-specific cytotoxic T lymphocytes
1 x 10e8 cells/m2 IV over 1 to 5 min
Other Name: EBV-specific cytotoxic T lymphocytes 1 x 108 cells/m2 IV

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   10 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  • Nasopharyngeal Carcinoma in first or subsequent relapse or with primary refractory disease in whom the EBV-genome or antigens have been demonstrated in tissue biopsy samples
  • Age 10 years or older
  • Life expectancy of 8 weeks or more
  • Karnofsky or Lansky score of 50 or more
  • Normal bilirubin level (per institutional standard)
  • AST and ALT 1.5 x or less upper limit of normal
  • Alk Phos level less than 2.5 x upper limit of normal
  • ANC greater than 1500 cells/ul
  • Hgb 8.0 or greater
  • Platelets 100,000 cells/ul or more
  • Creatinine 2 x or less ULN or GFR 50 ml/min/1.73 m2 or more
  • Women of child-bearing potential must take/use effective birth control while participating in the study.

EXCLUSION CRITERIA:

  • Due to the unknown effects of this therapy on a fetus, pregnant women will be excluded from this research.
  • Prior allergic reaction to the study drugs used in this protocol or other drugs formulated with polysorbate 80.
  • Known HIV positive subjects since treatment may be significantly immunosuppressive
  • Women who are breast-feeding
  • Severe intercurrent infection or uncontrolled condition
  • Patients, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00953420

Locations
United States, Texas
Houston Methodist Hospital
Houston, Texas, United States, 77030
Texas Children's Hospital
Houston, Texas, United States, 77030
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Texas Children's Hospital
The Methodist Hospital System
Center for Cell and Gene Therapy, Baylor College of Medicine
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Chrystal U Louis, MD, MPH Texas Children's Hospital; Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Chrystal Louis, Assistant Professor Pediatrics-Hem-Onc Cell & Gene, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00953420     History of Changes
Other Study ID Numbers: 25145-CADEN, CADEN
Study First Received: August 4, 2009
Last Updated: May 5, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:
nasopharyngeal carcinoma
Carboplatin
Docetaxel
Epstein-Barr Virus
T Lymphocytes
EBV-CTLs

Additional relevant MeSH terms:
Carcinoma
Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Docetaxel
Carboplatin
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on July 20, 2014